I. inflexus (Thunb.) Kudo extract improves atopic dermatitis and depressive-like behavior in DfE-induced atopic dermatitis-like disease.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease, which is caused by several genetic, immunological, and environmental factors. In addition to skin manifestations, AD is associated with an increased risk of depression and suicidal ideation. Furthermore, this association is underappreciated and therefore insufficiently studied. HYPOTHESIS/PURPOSE: We investigated the association between AD and depression and the effect of I. inflexus (Thunb.) Kudo extract (IIE) treatment in a Dermatophagoides farinae extract (DfE)-induced mouse model of AD. STUDY DESIGN: We evaluated the effects of IIE on depressive behavior in AD mice using four experimental groups: normal (untreated), AD mice (untreated Dfe-induced), IIE-treated (Dfe-induced AD mice), and positive control (tacrolimus-treated Dfe-induced AD mice). METHODS: An AD model was established by the application of 4% sodium dodecyl sulfate to the shaved dorsal neck skin and ears of NC/Nga mice 1 h before application of 100 mg DfE twice per week for 3 weeks. After the first week of DfE application, mice were treated with IIE every day for the remaining 2 weeks. We performed behavioral testing, histology, ELISA, and western blotting to assess depressive-like behavior and neuroinflammatory responses and to measure IgE, histamine, corticosterone, and serotonin levels. RESULTS: Compared with normal mice, AD mice showed more scratching behavior, increased ear swelling, and higher serum levels of IgE and histamine. AD mice also exhibited evidence of depressive-like behavior in the open-field and sucrose preference tests as well as altered serum corticosterone and brain serotonin concentrations. Histopathological analyses revealed increased infiltration of inflammatory cells and mast cells into the skin and ear tissue and elevated microglia activation and neuroinflammatory response in the brains of AD mice. Topical application of IIE reversed the effects of AD on scratching behavior, ear swelling, open-field locomotion, sucrose preference, and levels of IgE, histamine, corticosterone, serotonin, and inflammatory markers. Moreover, IIE treatment reduced inflammatory cytokine responses in keratinocyte cells. CONCLUSION: IIE is a candidate anti-AD therapy due to its ability to exert neuroprotective and antidepressant effects.

Gardenia jasminoides extract without crocin improved atopic dermatitis-like skin lesions via suppression of Th2-related cytokines in Dfe-induced NC/Nga mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a pruritic, chronic, relapsing inflammatory skin disease. Gardenia jasminoides extract (GJE) has been used as a traditional remedy for the treatment of various inflammatory diseases, including AD. The specific effects of the extract components, which include crocin, geniposidic acid, and gardenoside, on inflammatory responses in AD are not entirely clear. AIM OF THE STUDY: We determined the effects of G. jasminoides extract with crocin removed (GJE-C) on AD-like skin lesions in Dermatophagoies farina crude extract (Dfe)-treated NC/Nga mice, a well-known AD mouse model. MATERIALS AND METHODS: To prepare the mice, 150 µl of 4% sodium dodecyl sulfate (SDS) was applied to the shaved dorsal skin or ear of NC/Nga mice 1 h before application of 100 mg Dfe. After 7 d, GJE-C was applied every day for 14 d. We performed behavior, histological, ELISA, assays to evaluate chemokines, cytokines, and skin barrier proteins in skin or serum samples from treated and untreated NC/Nga mice. RESULTS: Topical application of GJE-C improved the severity scores of the AD-like skin lesions, frequency of scratching, and ear swelling in Dfe-treated NC/Nga mice similar to the complete GJE. In addition, GJE-C also reduced serum IgE and chemokine levels as well as the inflammatory response. Topical application of GJE-C also resulted in decreased infiltration of inflammatory cells, such as mast cells, via reduction of Th2 inflammatory mediators, including interleukin (IL)-4, IL-5, and IL-13, pro-inflammatory cytokines, and chemokines, and increased skin barrier protein expression in Dfe-treated NC/Nga mice. The GJE components geniposidic acid and gardenoside inhibited the production of atopic-related chemokines in HaCaT cells, but inclusion of crocin dampened this inhibition of chemokine production. CONCLUSIONS: Together, these findings indicate that GJE-C may improve AD-like lesions by inhibiting the Th2 inflammatory response and expression of chemokines while increasing the expression of skin barrier proteins. These data provide experimental evidence that GJE-C may harbor therapeutic potential for AD.